Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 +/- 0.29 SD and 0.10 +/- 0.03 nM, respectively, P < 0.001 for both) than in CHF (0.19 +/- 0.08 and 0.04 +/- 0.01), whereas no difference was detected between the mean levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1-20.5 nM, N = 4) in sheep with acute lung injury from intravenous Pseudomonas aeruginosa, but was undetectable in sheep with balloon-induced high left atrial pressure simulating CHF (N = 2) or control sheep (N = 2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25-95 pmol/h in sheep given P. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS.
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PMID:Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome. 142 25

One of the major target organs of hydrogen sulphide gas is the lung. Exfoliation of upper respiratory epithelia and pulmonary edema are prominent effects. Various neuropeptides contained in afferent C-fibres are intimately associated with the epithelia of the conducting airways and are liberated upon exposure to noxious gases. We sought to determine their role in the pathogenesis of hydrogen-sulphide-induced pulmonary injury by pretreating rats with the neurotoxin, capsaicin, which is known to ablate a subpopulation of vagal afferent C-fibres. Groups of capsaicin and saline (control) pretreated Fischer 344 rats were exposed to an edemogenic concentration of hydrogen sulphide (525-559 mg/m3) for 4 hr. Mortality was significantly greater (p less than 0.01) in the capsaicin treated rats (12/12) compared to the control animals (2/12). Pulmonary injury was also more severe in the capsaicin pretreated animals as assessed by lung water content, histological grade of pulmonary edema and protein in the broncho-alveolar fluid. Animals depleted of substance P exhibited a significantly greater (p less than 0.01) degree of bronchial epithelial cell exfoliation and ulceration following exposure to hydrogen sulphide. These experiments indicate that capsaicin sensitive sensory nerves may play a major role in pulmonary defense against the effects of inhaled toxic gases such as hydrogen sulphide.
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PMID:Capsaicin pretreatment modifies hydrogen sulphide-induced pulmonary injury in rats. 169 78

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.
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PMID:Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema. 170 92

This study was undertaken to evaluate the role of vagal nerves in the development of neurogenic pulmonary edema. We injected fibrinogen and thrombin into the cisterna magna of rats, a model of neurogenic pulmonary edema. When the vagal nerves were left intact, pulmonary edema occurred (fibrin-induced pulmonary edema) at a rate of 33%. Vagotomy at the midcervical portion increased the incidence of pulmonary edema to a rate of 100%, whereas pretreatment with atropine did not affect the incidence. These results suggested that vagal afferent nerves or nonadrenergic-noncholinergic efferent nerves played an important role in inhibiting the development of fibrin-induced pulmonary edema. Furthermore, in vagotomized and vagal nerve-intact rats pretreated with capsaicin, the incidence of pulmonary edema was 100%. Pretreatment with a substance P antagonist, [D-Pro2, D-Trp7,9]-SP, also increased the incidence to 100% in the vagal nerve-intact rats. On the other hand, intravenous administration of some neuropeptides that may be released from the capsaicin-sensitive nerves (e.g., substance P or calcitonin gene-related peptide) inhibited the development of pulmonary edema in vagotomized rats. We concluded that the vagal capsaicin-sensitive nerves exerted an inhibitory effect on the development of fibrin-induced pulmonary edema.
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PMID:Capsaicin-sensitive nerves exert an inhibitory effect on the development of fibrin-induced pulmonary edema in rats. 247 55

The modulatory role of histamine H3 receptors in pulmonary oedema induced by acetylcholine, capsaicin and by exogenous substance P was investigated in isolated, ventilated rabbit lungs. Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). Acetylcholine (10(-8) to 10(-4) M), substance P (10(-10) to 10(-6) M), capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) induced an increase in the Kf,c. Carboperamide, a novel histamine H3 receptor antagonist, induced a significant leftward shift of the concentration-response curve to acetylcholine and also enhanced the effect of capsaicin on the Kf,c, while it had no significant effect on the response to substance P and 5-HT. Imetit, a new histamine H3 receptor agonist, strongly inhibited the effects of acetylcholine and capsaicin. Imetit also strongly protected the lung against substance P effects but did not prevent the 5-HT-induced increase in the Kf,c. Carboperamide completely blocked the inhibitory effect of Imetit on the acetylcholine response. (R)-alpha-Methylhistamine, an other histamine H3 receptor agonist, had the same protective effect against acetylcholine response as Imetit. We conclude that histamine H3 receptors could protect the lung against acetylcholine- and capsaicin-induced oedema via a prejunctional modulatory effect on the C-fibres. However, since the response to exogenous substance P was also inhibited by histamine H3 receptor stimulation, the presence of such receptors at a postsynaptic level, probably on mast cells, was also suggested.
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PMID:Modulation of acetylcholine, capsaicin and substance P effects by histamine H3 receptors in isolated perfused rabbit lungs. 749 15

The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on hemodynamics and on pulmonary microvascular permeability were investigated in isolated, perfused rabbit lungs by measuring the arterial, capillary and venous pressures and the capillary filtration coefficient (Kf,c). CGRP was administered alone or in combination with capsaicin (10(-4) M), acetylcholine (ACh) (10(-11) M to 10(-7) M), substance P (SP) (10(-10) M to 10(-6) M) and serotonin (10(-4) M). The influence of a specific antagonist of CGRP receptors, CGRP8-37 (10(-8) M), on the pulmonary edema induced by these mediators was also considered. CGRP had no direct effect on the vascular pressures or on Kf,c. Capsaicin and serotonin induced an increase in Kf,c of 271 +/- 49% and 676 +/- 147% of base line, respectively. ACh and SP also increased the microvascular permeability, in proportion to the concentration. The effects of capsaicin, ACh and SP have been related to the activation of neurokinin NK1 receptors. Co-administration of CGRP with capsaicin and ACh enhanced the increase in Kf,c induced by these two drugs. By contrast, when co-injected with SP, CGRP inhibited the Kf,c increase induced by 10(-8) M and 10(-7) M of SP (P < .05) and significantly decreased the arterial and capillary pressures. CGRP also partly prevented the pulmonary edema induced by serotonin (P < .05). Pretreatment with CGRP8-37 partly prevented the effects of capsaicin and ACh on Kf,c but bestowed no protection against SP-induced pulmonary edema. These data suggest that CGRP is co-released with SP from the C-fibers upon the action of capsaicin and ACh in the rabbit lung. Because CGRP potentiated the pulmonary edema induced in capsaicin and ACh, but decreased the effects of SP, we hypothesize that CGRP exerts a positive retro-control on the release of neuropeptides by these fibers but can attenuate their effects on the target cells.
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PMID:Modulation of the acetylcholine- and substance P-induced pulmonary edema by calcitonin gene-related peptide in the rabbit. 751 13

1. The modulatory role of neuropeptide Y (NPY) on pulmonary oedema induced by acetylcholine and capsaicin was investigated. The effects of NPY on the haemodynamic response to acetylcholine, phenylephrine and substance P were also investigated. 2. Isolated, ventilated, exsanguinated lungs of the rabbit were perfused with a constant flow of recirculating blood-free perfusate. The double/arterial/venous occlusion method was used to partition the total pressure gradient (delta Pt) into four components: the arterial gradient (delta Pa), the pre- and post-capillary gradients (respectively delta Pa' and delta Pv') and the venous pressure gradient (delta Pv). Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). 3. Acetylcholine (10(-8) M to 10(-4) M) and substance P (SP, 10(-10) M to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) also increased this parameter. NPY (10(-8) M) completely inhibited the effects of acetylcholine and capsaicin on the Kf,c, without preventing the effects of substance P and 5-HT. 4. Acetylcholine induced concentration-dependent vasoconstriction in the precapillary segment. The effect was inhibited by NPY and aspirin, an inhibitor of cyclo-oxygenase, while ketanserin, a 5-HT2 receptor antagonist, and SR140333, a new NK1 antagonist, had no protective effect. Phenylephrine increased delta Pa at high concentration, an effect also inhibited by NPY and aspirin. Substance P had no significant haemodynamic effect. When injected together with NPY, substance P (10(-6) M) induced a significant increase in the total pressure gradient. 5. It was concluded that NPY can protect the lung against acetylcholine- and capsaicin-induced oedemavia a prejunctional modulatory effect on the C-fibres. NPY also inhibits acetylcholine-evoked precapillary and phenylephrine-induced arterial vasoconstriction, probably by interfering with cyclo-oxygenase products synthesis.
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PMID:Modulatory effect of neuropeptide Y on acetylcholine-induced oedema and vasoconstriction in isolated perfused lungs of rabbit. 753 83

We examined the relationship between airway obstruction and plasma extravasation produced by the intravenous administration of the selective NK1 receptor agonist [Sar9, Met(O2)11]-substance P(SP). Conscious guinea-pigs were injected with Evans' blue dye followed by intravenous [Sar9,Met(O2)11]-SP. Animals were killed 3 min later and airway obstruction, determined via excised lung gas volumes, and plasma extravasation in the trachea, mainstem bronchi and intrapulmonary airways quantitated. Maximal plasma protein extravasation occurred at a dose about 30 times less than that required to elicit airway obstruction. Neither the neutral endopeptidase (NEP) inhibitor, thiorphan, or the angiotensin-converting enzyme (ACE) inhibitor, captopril, altered the extravasation response to [Sar9,Met(O2)11]-SP. However, thiorphan alone or combined with captopril produced a small but significant potentiation of the airway obstructive response. The marked difference between pulmonary gas trapping and Evans' blue extravasation responses suggest that [Sar9,Met(O2)11]-SP-induced airway obstruction is not secondary to increased pulmonary edema.
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PMID:Pulmonary actions of the neurokinin1-specific agonist [Sar9,Met(O2)11]-substance P. 753 2

The modulatory role of endogenous nitric oxide (NO) on pulmonary edema induced by acetylcholine (ACh), capsaicin, substance P (SP) and 5-hydroxytryptamine (5-HT) was investigated by using an inhibitor of NO synthase, N-omega-nitro-L-arginine (L-NNA). The effects of endogenous NO on the hemodynamic response to ACh, 5-HT and SP were also investigated. The capillary filtration coefficient (Kf,c), the total pressure gradient (delta Pt) and its four components [arterial (delta Pa), pre- (delta Pa') and post-capillary (delta Pv'), and venous gradient (delta Pv)] were evaluated on isolated, ventilated, perfused rabbit lungs. ACh (10(-8) to 10(-4) M) and SP (10(-10) to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-HT (10(-4) M) also increased this parameter. L-NNA (10(-4) M) completely inhibited the effects of ACh and capsaicin on the Kf,c, without preventing the effects of SP and 5-HT. ACh induced a concentration-dependent vasoconstriction in the precapillary segment. Pretreatment with L-NNA enhanced this increase in delta Pa' but also increased delta Pv' and delta Pv. 5-HT increased delta Pt and delta Pa proportionally to the concentration. This effect was enhanced by L-NNA, which also increased delta Pa'. SP had no significant hemodynamic effect. Pretreatment with L-NNA did not modify the response to SP. Sodium nitroprusside (10(-5) M) induced a left shift of the concentration-response curve to ACh on the Kf,c, although it did not change the response to SP. Sodium nitroprusside also inhibited the hemodynamic effect of ACh. It was concluded that endogenous NO is involved in ACh-and capsaicin-induced edema via a prejunctional stimulatory effect on the C-fibers. Endogenous NO can also modulate ACh- and 5-HT-induced vasoconstriction by exerting a vasodilator action on the whole pulmonary vascular bed.
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PMID:Endogenous nitric oxide modulates acetylcholine-induced edema and vasoconstriction in isolated perfused rabbit lungs. 754 68

The frequent occurrence of acute death from pulmonary failure in experimental head injury studies on Sprague-Dawley rats prompted an investigation into the manner in which acute neurogenic pulmonary edema develops in these animals as a result of an applied fluid pressure pulse to the cerebral hemispheres. Studies were performed in adult animals using histamine H1 and H2 blocking agents, or in adult animals treated as neonates with capsaicin to destroy unmyelinated C-fibers. Recordings were made of either the pulmonary arterial or the right ventricular pressure, and the left atrial and femoral arterial pressures before, during, and after injury to provide a record of the hemodynamic response throughout the development of neurogenic pulmonary edema. Head injury triggered the almost immediate development of pressure transients with and without neurogenic pulmonary edema. All rats, regardless of treatment, reacted with nearly identical systemic arterial pressure responses; however, the pulmonary responses followed a time course that was independent of systemic arterial pressure changes. Acute neurogenic pulmonary edema was always associated with a substantial increase in pulmonary arterial and left atrial pressures; conversely, pressure increases of similar magnitude were not always associated with edema. Histamine H1 and H2 blockers significantly reduced the pulmonary pressure surges only in rats free of neurogenic pulmonary edema. All capsaicin-treated rats showed suppressed pulmonary pressure responses, normal lung water content, elevated lung surface tension, and significantly reduced levels of immunoreactive substance P in the spinal cord and vagus nerve. While the pressures cannot clarify how edema influences the observed hemodynamics, they do not support the view that edema is the direct consequence of pulmonary hypertension. It is proposed that neurogenic pulmonary edema is a functional disturbance provoked by adverse stimuli from outside the lungs and that in the rat the primary afferent fiber is essential to the production of this entity.
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PMID:Effect of neonatal capsaicin treatment on neurogenic pulmonary edema from fluid-percussion brain injury in the adult rat. 768 Jul 9


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